In situ hybridization studies demonstrate a decrease in prodynorphin mRNA in dentate granule cells of gerbil hippocampus following transient ischemia. Quantitative assessment by means of grain counts following autoradiography indicate a decrease of approximately 50% at 24h recirculation, comparable to the decreases in dynorphin peptide immunoreactivity in hippocampal extracts observed in previous studies. This down regulation of dynorphin synthesis at the transcriptional level is similar to that described by other investigators following seizures, and is consistent with an increased activation of hippocampal circuitry following ischemia. In view of the concurrent induction of c-fos and hsp7O in this cell population, altered synthesis of opioid peptide precursors would appear to be another component of what is coming to be understood as a complex pathophysiological response of neurons to ischemia and other stresses.